E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Mild to moderate distal subungual Onychomycosis due to Dermatophytes. |
|
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 11.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10030338 |
E.1.2 | Term | <Manually entered code. Term in E.1.1> |
|
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate the effect of different doses of P-3058 compared to placebo in the treatment of onychomycosis after 52-week treatment |
|
E.2.2 | Secondary objectives of the trial |
•To evaluate the shape and the location of the dose response-curve of the efficacy outcome (responders rate).
•To determine the maximal dose beyond which additional benefit would be unlikely to occur |
|
E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
“Pharmacokinetics evaluation in blood and nail samples of 3 doses of P-3058 nail lacquer (5% o.d., 10% o.d., and 10% o.w.) given for 52 weeks in patients with onychomycosis”. TO BE DONE ONLY IN LATVIA.
Final version: 2008/09/30
Objective: to evaluate nail concentrations and systemic exposure to the test products after multiple applications in a long-term study.
|
|
E.3 | Principal inclusion criteria |
• Written informed consent before starting any study related procedures • Patients aged ≥12 up to 80 years old • Males or females •Outpatients •Patients with established clinical diagnosis of mild-to-moderate distal sub-ungual onychomycosis (i.e. involving ≥ 25% to ≤ 60% of the distal bed-adherent nail plate without involvement of the lunula) caused by dermatophytes, affecting at least one big toenail •Patients with positive KOH examination from the target big toenail obtained at screening •Patients with positive culture for only dermatophyte/s in screening nail sample
|
|
E.4 | Principal exclusion criteria |
•Patients with history of cardiovascular, renal, neurologic, liver, immunologic or endocrine dysfunction if they are clinically significant. •Patients with a recent history (< 1 year) of myocardial infarction and/or (< 3 years) of heart failure or patients with any cardiac arrhythmia requiring drug therapy •Patients with liver function impairment AST, ALT more than twice above the upper limit of reference range •Patients with kidney function impairment serum creatinine more than twice above the upper limit of reference range •History of cancer within the past 5 years, excluding treated basal cell carcinoma •Chemotherapy, immunosuppressive therapy in the 12 weeks prior to screening visit •Systemic glucocorticosteroids, antimetabolites and immunostimulants therapy in the 4 weeks prior to screening visit •Alcohol or substance abuse •HIV infection or any other immunodeficiency •Patients unable to understand the procedures and purposes of the study •Patients with history of allergic reactions to terbinafine or its excipients •Use of an investigational drug or participation in an investigational study within 30 days prior to administration of study medication •Patients using nail polish or other nail cosmetic product on the concerned nails from at least 24 hours prior to study drug administration until the end of the study •Patients with target nail hyperkeratosis exceeding 4 mm in thickness •Patients with proximal subungual involvement •Disease involving <25% or >60% of distal bed-adherent nail plate •Patients with mucocutaneous candidiasis •Patients with white superficial onychomycosis •Patients with onychomycosis caused by yeasts or non-dermatophytes mould •Patients with "Yellow spikes" on the target nail •Patients with lunula involvement •Patients with negative KOH examination at screening •Patients with severe plantar or moccasin tinea pedis •Patients with nail abnormalities due to conditions like psoriasis or lichen planus •Patients with uncontrolled diabetes •Patients with recurrent erysipela at screening visit •Use of systemic antifungal drugs in the 6 months prior to screening visit •Use of topical products containing terbinafine in the 3 months prior to screening visit •Use of topical antifungal drugs (other than terbinafine) in the four weeks prior to screening visit •Breast-feeding patients •Positive urine pregnancy test at screening (performed to all females of child bearing potential or being in non surgical post-menopause for less than 1 year) •Women of child-bearing potential or in menopause for less than 1 year not using a reliable method of contraception.
|
|
E.5 End points |
E.5.1 | Primary end point(s) |
The primary end-point is the responders rate as evaluated by the central, blinded Assessor at week 52 (end of treatment) This is defined as patients with conversion to negative of culture and of microscopic KOH examination and with decrease of affected nail area to ≤10% of total.
Secondary efficacy end-points: •Cure rate defined as complete replacement of the affected nail by new healthy nail, as evaluated by a central, blinded Assessor, accompanied by conversion to negative of culture and of microscopic KOH examination at week 16, 28, 40, 52 (end of treatment), 64 and 76 •Conversion to negative of culture at week 4, 16, 28, 40, 52, 64 and 76 •Conversion to negative of microscopic finding on KOH preparation at week 4, 16, 28, 40, 52, 64 and 76 •Determination of growth rate of healthy nail at week 16, 28, 40, 52, 64 and 76 by the central, blinded Assessor •Responders as evaluated by the central, blinded Assessor at week 16, 28, 40, 64 and 76 •Responders as evaluated by the local Investigator at week 16, 28, 40, 52, 64 and 76 •Decrease of the affected nail area to ≤ 10% of the total at week 4,16, 28, 40, 52, 64 and 76 •Time to reach the efficacy outcome responder •Time to reach the efficacy outcome cure •Rate of relapse at week 76 (at least one among the following: affected target nail area >10%, culture positive, KOH positive), in patients “cured” at week 52 •Acceptance of therapy by patient •Overall safety evaluation
|
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 25 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
| |
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |